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. 2014 Apr;9(4):483-7.
doi: 10.1097/JTO.0000000000000125.

Clinical significance of BIM deletion polymorphism in non-small-cell lung cancer with epidermal growth factor receptor mutation

Kazutoshi Isobe  1 , Yoshinobu Hata, Naobumi Tochigi, Kyohei Kaburaki, Hiroshi Kobayashi, Takashi Makino, Hajime Otsuka, Fumitomo Sato, Fumiaki Ishida, Naoshi Kikuchi, Nao Hirota, Keita Sato, Go Sano, Keishi Sugino, Susumu Sakamoto, Yujiro Takai, Kazutoshi Shibuya, Akira Iyoda, Sakae Homma
Affiliations
Free PMC article

Clinical significance of BIM deletion polymorphism in non-small-cell lung cancer with epidermal growth factor receptor mutation

Kazutoshi Isobe et al. J Thorac Oncol. 2014 Apr.
Free PMC article

Abstract

Background: Germline alterations in the proapoptotic protein Bcl-2-like 11 (BIM) can have a crucial role in tumor response to treatment. To determine the clinical utility of detecting BIM deletion polymorphism in non-small-cell lung cancer positive for epidermal growth factor receptor (EGFR) mutation, we examined outcomes of patients with and without BIM alterations.

Methods: We studied 70 patients with EGFR mutation-positive non-small-cell lung cancer who were treated with an EGFR tyrosine kinase inhibitor between January 2008 and January 2013. BIM deletion was analyzed by polymerase chain reaction in 58 samples of peripheral blood and 24 formalin-fixed paraffin-embedded slides of surgical specimens (20 of lung tissue and four of brain tissue); both blood and tissue specimens were available for 12 patients. We retrospectively analyzed clinical characteristics, response rate, toxicity, and outcomes among patients with and without BIM deletion.

Results: BIM deletion was present in 13 of 70 patients (18.6%). There were no significant differences between patients with and without BIM deletion in clinical characteristics, rate of response to EGFR tyrosine kinase inhibitor, or incidence of adverse events. Patients with BIM deletion had significantly shorter progression-free survival (PFS) than those without BIM deletion (median, 227 versus 533 days; p < 0.001). Multivariate Cox regression analysis showed that BIM deletion was an independent indicator of shorter PFS (hazard ratio, 3.99; 95% confidence interval, 1.864-8.547; p < 0.001).

Conclusions: Polymerase chain reaction successfully detected BIM deletion in samples of peripheral blood and formalin-fixed paraffin-embedded slides of surgical specimens. BIM deletion was the most important independent prognostic factor in shorter PFS.

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Conflict of interest statement

Disclosure: The authors declare no conflict of interest.

Figures

FIGURE 1.
FIGURE 1.
Patients with BIM deletion polymorphism had significantly shorter progression-free survival than did those without BIM deletion polymorphism (median, 227 versus 533 days; p < 0.001).
FIGURE 2.
FIGURE 2.
There was no significant difference in overall survival between patients with and without BIM deletion polymorphism (median, 1176 versus 1363 days; p = 0.27).
See this image and copyright information in PMC

References

    1. Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004;350:2129–2139. - PubMed
    1. Paez JG, Jänne PA, Lee JC, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004;304:1497–1500. - PubMed
    1. Shigematsu H, Lin L, Takahashi T, et al. Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. J Natl Cancer Inst. 2005;97:339–346. - PubMed
    1. Bell DW, Lynch TJ, Haserlat SM, et al. Epidermal growth factor receptor mutations and gene amplification in non-small-cell lung cancer: molecular analysis of the IDEAL/INTACT gefitinib trials. J Clin Oncol. 2005;23:8081–8092. - PubMed
    1. Ettinger DS, Akerley W, Bepler G, et al. NCCN Non-Small Cell Lung Cancer Panel Members. Non-small cell lung cancer. J Natl Compr Canc Netw. 2010;8:740–801. - PubMed

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